The purpose of this study is to define the role ot titin in the structure and function of cardiac and skeletal muscle myofibrils. This protein, which has been reported to constitute as much as 10% of skeletal and 18% of cardiac myofibrils, has a subunit size in excess of 1,000,000 daltons. Studies are currently in progress to define the location of titin in the myofibril using monoclonal antibodies. Both fluorescence labeling on intact and partially extracted myofibrils and immunoelectron microscopic studies will be conducted. Attempts will be made to determine whether thick or thin filaments bind to isolated titin or whether other specific proteins (such as desmin, Alpha-actinin, myomesin, nebulin, etc.) may interact. Studies will be conducted to determine the relationship of titin appearance to myofibrillogenesis. The precise amount of titin in skeletal and cardiac myofibrils which have been purified on Percoll gradients will be analyzed. Changes in titin properties with age will be examined in normal and cardiomyopatihic hamster hearts. The elastic nature of titin and the apparent relationship between the high resting tension of cardiac muscle and the high titin content suggests it may play a key role in cardiac function. Changes and/or damage to titin may well be involved in the alterations occurring after a heart attack or in congestive heart failure.